Cellular & Molecular Immunology. 2004 Feb, Vol.1, No.1, pp.31-36.
Immunotherapy with Agonistic Anti-CD137: Two Sides of a Coin

Yonglian Sun¹, Jonathan H. Chen¹ and Yangxin Fu^{1, 2
1}The Department of Pathology and Committee in Immunology, The University of Chicago, Chicago, Illinois, USA.
²Corresponding to: Dr. Yangxin Fu, Deptartment of Pathology, MC3083, 5841 S. Maryland, J541, The University of Chicago, Chicago, IL 60637, USA. Tel: +773-702-0929; Fax: +773-834-8940; E-mail: yfu@midway.uchicago.edu.

CD137 (4-1BB), a member of the TNF receptor superfamily, is an inducible T cell costimulatory receptor primarily expressed on activated CD4+ and CD8+ T cells. Agonistic monoclonal antibodies (mAbs) against CD137 greatly enhance T cell-mediated immune responses against many types of tumors and viruses. Surprisingly, these agonists also showed therapeutic effects in several autoimmune diseases. These findings suggest that in different disease environments, CD137 engagement with agonist mAb in vivo can diametrically modulate immune response outcomes. Therefore, CD137 agonists represent a promising immunotherapeutic approach to a wide array of disparate immune disorders. However, CD137’s potency in modulating immune response necessitates caution when targeting CD137 clinically.